Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (3): Kinetoplastids

Abaza, Sherif za

doi:10.21608/puj.2019.20020.1055

Cited by 2 publications

(2 citation statements)

References 201 publications

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“…Due to its significant role in T. cruzi survival and virulence in both the host and vector, CRZ was suggested as a promising drug target and vaccine candidate. Its crystal structure was identified and several studies were conducted for development of selective CRZ inhibitor (reviewed by Abaza [78] ). A combination of two synthesized oxyguanidine analogs (WRR-483, and WRR-669) was established as an approved novel drug for chronic Chagas disease [79,80] .…”

Section: [Iii] Pathogenesis and Virulence 1 Proteasesmentioning

confidence: 99%

Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part II: Parasite targets

Abaza

2022

Parasitologists United Journal

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Growth and replication (DNA synthesis and gene expression) 1. Nucleic acids synthesisNucleotides serve as monomeric units of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). They are formed of a nitrogenous base (nucleoside), five-carbon sugars (ribose or deoxyribose), and a phosphate group (1-3 phosphates). Accordingly, they are termed monophosphate (MP), diphosphate (DP), and triphosphate (TP), respectively. Symthesis of DNA and RNA copies requires supply of two nitrogenous bases (purines and pyrimidines) in similar quantities. As long as both bases are available, synthesis is self-activated, and when there are no more bases, the synthesis is self-inhibited. While purines include adenine (A), and guanine (G), pyrimidines include cytosine (C), thymine (T), and uracil (U). Notably, DNA is formed of two purines (A and G), and two pyrimidines (C and T), while (U) replaces (T) in RNA. Nucleotides have several cellular functions including growth and replication via synthesis of DNA and RNA signaling pathways since they are involved in synthesis of intracellular cyclic second messengers (cAMP, and cGMP). They are energy sources due to involvement of nitrogenous bases in the components of nucleoside TPs (ATP, GTP, TTP, CTP, and UTD). Energy is required for protein and cell membrane syntheses, cell division, and motility. Moreover, adenine contributes in formation of several cofactors required for enzymatic reactions such as coenzyme A, nicotinamide adenine dinucleotide (NAD), NAD phosphate (NADP), flavine adenine dinucleotide (FAD) and flavine mononucleotide (FMN). Lastly, uracil diphosphate (UDP) is utilized in glucogenesis; a ubiquitous metabolic pathway required for production of glucose from non-carbohydrate carbon substrates [2] .Synthesis of purine and pyrimidine nucleotides is either de novo or through a salvage pathway. In such a pathway, nucleoside transporters (NTs), known also as permeases, carry salvaged bases and nucleosides across parasite plasma membrane to synthesize nucleotides. Therefore, nucleoside transporters and enzymes involved in purine or pyrimidine synthesis, either de novo or via salvage pathways contributing to nucleic acid processing, are potential drug targets.Transporters: There are four balanced NTs (ENTs). While ENT1 and ENT2 are the major

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Section: [Iii] Pathogenesis and Virulence 1 Proteasesmentioning

confidence: 99%

Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part II: Parasite targets

Abaza

2022

Parasitologists United Journal

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“…Currently, several tools are being used in the development of vaccines in the context of trypanosomatids, such as immunoinformatic, genomic, and proteomic techniques that mainly contribute to the identification of new antigenic targets and epitopes of these parasites [ 31 , 32 ], as well as in the development of various immunization protocols in experimental models [ 33 , 34 , 35 , 36 , 37 , 38 ]. Several proteins and virulence factors are biologically and structurally shared among protozoa of the trypanosomatid family and therefore could be used as possible targets for the development of vaccines, such as surface glycoproteins [ 39 , 40 , 41 ], cysteine proteases [ 42 , 43 ], and metalloproteases [ 44 , 45 , 46 ].…”

Section: Vaccines To Control Diseases Caused By Trypanosomatids: Wmentioning

confidence: 99%

VLP-Based Vaccines as a Suitable Technology to Target Trypanosomatid Diseases

et al. 2021

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Research on vaccines against trypanosomatids, a family of protozoa that cause neglected tropical diseases, such as Chagas disease, leishmaniasis, and sleeping sickness, is a current need. Today, according to modern vaccinology, virus-like particle (VLP) technology is involved in many vaccines, including those undergoing studies related to COVID-19. The potential use of VLPs as vaccine adjuvants opens an opportunity for the use of protozoan antigens for the development of vaccines against diseases caused by Trypanosoma cruzi, Leishmania spp., and Trypanosoma brucei. In this context, it is important to consider the evasion mechanisms of these protozoa in the host and the antigens involved in the mechanisms of the parasite–host interaction. Thus, the immunostimulatory properties of VLPs can be part of an important strategy for the development and evaluation of new vaccines. This work aims to highlight the potential of VLPs as vaccine adjuvants for the development of immunity in complex diseases, specifically in the context of tropical diseases caused by trypanosomatids.

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Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (3): Kinetoplastids

Cited by 2 publications

References 201 publications

Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part II: Parasite targets

Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part II: Parasite targets

VLP-Based Vaccines as a Suitable Technology to Target Trypanosomatid Diseases

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